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GSE15293
Mus musculus
34 Downloadable Samples
Description
Aim of present study was to describe the changes induced deletion of the Wfs1 gene in the temporal lobe of mice. Mutant mice were backcrossed to two different genomic backgrounds in order to exclude confounding foreign genomic background influence. Samples from temporal lobes were analyzed by using Affymetrix Genechips, expression profiles were functionally annotated by using GSEA and Ingenuity Pathway Analysis. We found that Wfs1 mutant mice are significantly smaller (20.9 1.6 g) than their wild-type counterparts (31.0 0.6g, p < 0.0001). Interestingly, genechip analysis identified growth hormone transcripts up-regulated and functional analysis found appropriate pathways activated. Moreover, we found significant increase in the level of IGF1 in the plasma of wfs1 mutant mice. Taken together, wfs1 mutation induces growth retardation whereas the growth hormone pathway is activated. Further studies are needed to describe biochemical and molecular details of the growth hormone axis in the wfs1 mutant mice.
Publication Title
Wfs1 gene deletion causes growth retardation in mice and interferes with the growth hormone pathway.
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Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Mammalian genomes contain numerous DNA elements with potential transcription regulatory function but unknown target genes. We used transgenic, gain-of-function mice with an ectopic copy of the beta-globin locus control region (LCR) to better understand how regulatory elements dynamically search the genome for target genes. We find that the LCR samples a restricted nuclear sub-volume in which it forms preferential contacts with genes controlled by shared transcription factors. One contacted gene, betah1, located on another chromosome, is upregulated, providing genetic demonstration that mammalian enhancers can function between chromosomes. Upregulation is not pan-cellular but confined to selected jackpot cells significantly enriched for inter-chromosomal LCR-betah1 interactions. This implies that long-range DNA contacts are relatively stable and cell-specific and, when functional, cause variegated expression. We refer to this as spatial effect variegation (SEV). The data provide a dynamic and mechanistic framework for enhancer action, important for assigning function to the one- and three-dimensional structure of DNA.
Publication Title
Variegated gene expression caused by cell-specific long-range DNA interactions.
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Sample Metadata Fields
Specimen part, Disease
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